Accupril

For all the people who succumb to heart disease each year--some 927,000 in 2002, according to the American Heart Association. There is still a significant gap between people who have been diagnosed with heart disease and those who don't know they have it--a group that continues to grow.

Millions of Americans are changing their lifestyles, assuming heart-healthy diets and activities and taking prescription medicines to lower their cholesterol or blood pressure--two key cardiovascular disease risk factors. But that's not enough. There are other risk factors for heart disease that are being overlooked. According to a just-released 2005 update of the American Heart Association's heart disease and stroke statistics, those risk groups include:

* smokers--some 49 million Americans

* people who have a family history of heart disease

* people with diabetes--roughly 20 million Americans

* obese or significantly overweight people, who now number 63 million Americans

* patients with either high blood pressure (65 million with blood pressure over 140/90) or high cholesterol (106.9 million with total cholesterol above 200 mg/dL).

But more people are at risk than realize it. "Very few people have none of those [risk factors]," said Edward Winslow, cardiologist and associate professor of clinical medicine at Northwestern University's Feinberg School of Medicine.

Add the number of people at risk for some type of heart condition to the 70 million Americans who already have the disease, and that presents an extremely sizeable potential market.

The obvious market potential for products to treat heart disorders has prompted drug makers to launch potential blockbusters successfully, including AstraZeneca's lipid-lowering statin Crestor and the combination drugs Vytorin from Merck/Schering-Plough and Pfizer's Caduet. Another 120 potentially big-selling drugs to treat heart disease are in the research and development pipeline.

Drug makers are still missing much of the potential market opportunity in the heart-health treatment category. Heart disease has been the leading cause of death for Americans every year since 1900, except 1918, the year of the Spanish flu pandemic. While seniors may be interested in taking a prophylactic approach to health matters--baby boomers are looking for ways to stay active later in their lives, after all--the sedentary, fast-food lifestyle of Americans is not conducive to a preventative approach to health care. Of the 70 million Americans who have had a close encounter with heart disease, 43 million are younger than 65. It's not exclusively an old person's disease.

For people who have established heart disease, there are four classes of medications that doctors can prescribe, Winslow said. Among them:

* aspirin or Plavix (clopidogrel), with aspirin being the more desirable option, Winslow said, to prevent blood clotting.

* beta blockers like atenolol, metoprolol and propranolol, which have been demonstrated to block the effects of adrenaline on beta receptors, thereby slowing the nerve impulses that travel through the heart. As a result, the heart needs less blood and oxygen.

* statins, which help lower low-density lipoproteins. Last summer, the National Cholesterol Education Program recommended a target LDL level of 70 for patients at a very high risk of heart disease, down from 100. Under previous guidelines, 36 million people qualified for statin therapy, while upper estimates on actual statin use were just above 15 million.

* angiotensin-converting enzyme inhibitors, which reduce blood pressure. These medicines include King Pharmaceutical's Altace and Pfizer's Accupril.

Add to those therapies a new class of drugs on the horizon that one day may be used to better manage lipid profiles. The new medicines, called cholesteryl ester transfer protein inhibitors, are intended to raise HDL levels--the good cholesterol--and to lower LDL levels.

Initial trials have proven promising. While at least three companies--Avant Immunotherapeutics, Roche and Pfizer--are developing drugs in that class, it will be some time before a CETP inhibitor is approved for use. Trial results for the projected first-to-market, Pfizer's torcetrapib and Lipitor combo, could be available by 2007. But even if Pfizer filed a new drug application in 2007, the drug wouldn't be approved before 2008.

The practice of combining established drugs to create new products like Vytorin and Caduet provides drug makers a promising new method to treat heart disease and to extend the lifecycle of a drug.

However, combination drugs hold less promise for doctors and pharmacists. For doctors, combination drugs force a specific regimen with specific doses into their treatment scenarios. For example, while Vytorin, a combination of Schering-Plough's Zetia and Merck's Zocor, has been shown to lower cholesterol better than both Lipitor and Zocor alone, many doctors may still prefer to prescribe a combination of Zetia and the statin Lipitor. "The perceived value is that it is a single pill, and the Vytorin combination or even putting Zetia with Lipitor would give you a greater cholesterol reduction, and it should be safe," Winslow said.

However, according to Merck, the drug's efficacy is driving doctors to prescribe Vytorin. As many as 80 percent of patients whose doctors switched them to Vytorin from another therapy were switched because of a potential improvement in outcomes versus perceived convenience, the company reported.

For pharmacies, Vytorin represents one prescription dispensed when there may have been two previously. But even that simple math may not add up, Merck noted. The company stated that prescriptions continued to grow for Zetia even after the introduction of Vytorin, suggesting that pharmacies are not losing prescriptions; they're gaining them.

Caduet is an interesting combination therapy in that it combines a calcium channel blocker, Norvasc, for treating high blood pressure and the statin Lipitor, making it the first combination drug to treat two separate disease states. According to Pfizer, of the 63 million Americans with dyslipidemia and the 47 million with hypertension, some 30 million shake out as at risk for both high cholesterol and high blood pressure.

Although Pfizer has generated only $34 million in sales since the drug's approval in February, analysts have predicted Caduet's worldwide sales could reach $1.1 billion by 2008.

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